position paper: global recommendations for the management ... fileinnovations-2 • assigning...
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An International Atherosclerosis Society
Position Paper:
Global Recommendations for the
Management of Dyslipidemia
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Innovations-1
• International position paper based on multiple
lines of evidence
• Identification of non-HDL-cholesterol (non-HDL-C)
as a major form of atherogenic cholesterol
• Definition of atherogenic cholesterol as either
LDL-cholesterol (LDL-C) or non-HDL-C
• Definition of optimal levels of atherogenic
cholesterol (both LDL-C and non-HDL-C) for
primary and secondary prevention
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Innovations-2
• Assigning priority to long-term risk categories
over short-term risk
• Adjustment of risk estimation according to
baseline risk of different nations or regions
• Primary emphasis on lifestyle intervention;
secondary emphasis on drug therapy
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
International Position Paper
• Primary prevention
– Randomized controlled trials
– Epidemiology
– Genetics
– Other lines of evidence
• Secondary prevention
– Mainly randomized controlled trials
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Purposes of Position Paper
• To amplify existing national guidelines
• Not to replace national guidelines
• To offer an international frame work for future
guideline development
• To provide a simplified approach to dyslipidemia
management
• To emphasize lifestyle approaches to prevention
of cardiovascular diseases
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
LDL-C and Non-HDL-C
as Targets of Therapy
• LDL: major atherogenic lipoprotein
• VLDL: additional atherogenic lipoprotein
• Non-HDL: LDL + VLDL
• LDL cholesterol (LDL-C): traditional primary
target for clinical intervention
• Non-HDL cholesterol (Non-HDL-C): appropriate
target for clinical intervention
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Advantages of Non-HDL-C as
Target for Clinical Intervention
• Sum of all atherogenic lipoproteins (LDL+ VLDL)
• Does not require fasting for accurate
measurement
• Subsumes most cases of elevated triglycerides
• Growing evidence for greater predictive power
than LDL-C
• Essentially equivalent to apolipoprotein B in
predictive power
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Atherogenic Cholesterol
• Either LDL-C or non-HDL-C
• LDL-C is a traditional primary target of
lipid-lowering therapy
– Many national guidelines identify LDL-C as
the target of treatment
• Non-HDL-C is increasingly preferred as
the target of therapy
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Optimal Levels of LDL-C and Non-
HDL-C for Primary Prevention
• Optimal levels
– LDL-C < 100 mg/dL (2.6 mmol/L)
– Non-HDL-C < 130 mg/dL (3.4 mmol/L)
• Optimal levels not goals of therapy
• Cholesterol-lowering goals determined by
clinical judgment
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Identifying Persons at Long-term
Risk for ASCVD
• Long-term risk takes precedence over
short-term risk for decisions about
dyslipidemia intervention
• Long-term risk = risk to age 80 years
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Factors Affecting Long-term Risk
for ASCVD
• Atherogenic lipoproteins (LDL & VLDL) initiate
and promote atherogenesis
– Alone can cause premature ASCVD
• Other risk factors accelerate atherogenesis
– Cigarette smoking
– Hypertension
– Diabetes
– Low HDL
– Genetics (family history)
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Levels of Long-term Risk for
ASCVD (up to age 80)
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Risk Level Total Risk
High > 45%
Moderately high 30-44%
Moderate 15-29%
Low < 15%
Lloyd-Jones/Framingham Risk
Algorithm
Cholesterol (mg/dL) 180-199 200-239 > 240
Systolic BP (mmHg) 120-139 140-159 > 160
Cigarette smoking 0 0 +++
Diabetes 0 0 +++
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Risk for CVD Morbidity by Age 80*
Risk Factor Men Women
None 5% 8%
> 1 minor 25% 10%
> 1 moderate 38% 22%
1 major 45% 25%
> 2 major 60% 45%
* For United States
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Framingham Heart Study
Recalibration Coefficients for CHD
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Cohort Combined M & F Cohort Male Female
Australia 0.90 Britain 0.57
France 0.41 Switzerland 0.48 0.44
Germany 0.43
Ireland 0.76
Italy 0.37
NE Spain 0.37
New Zealand 1.15
Scotland 0.91
UK 0.76
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Cohort Male Female
China 0.36
Japanese American 0.50
Korean 1.02 0.96
Native American 0.80 0.70
Rural India 1.0 0.8
Urban India 1.81 1.54
Framingham Heart Study
Recalibration Coefficients for CHD
Qualitative High-Risk Conditions
• Familial hypercholesterolemia
• Diabetes + other risk factors
• Chronic kidney disease
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Long-term Risk Algorithms
• Lloyd-Jones/Framingham
– Adjustments for specific countries
• QRISK
– Developed for UK
• Adjustments for ethnicity
– May apply to Western Europe
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
IAS Recommendations for Cholesterol-Lowering Therapy at Different Risk Levels
Risk Level
to Age 80s
Low
(< 15%)
Moderate
(15-24%)
Moderately
High
(25-40%)
High
(> 40%)
Therapeutic
Intensity
Moderate Moderately
High
High
Specific
Therapy
Public
health
guidelines
MLT
+CLD
optional
MLT
+CLD
consideration
MLT
+CLD
Indicated
MLT = Maximal lifestyle therapy CLD = Cholesterol-lowering drug
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Optimal Levels of Atherogenic
Cholesterol vs. Goals of Therapy
• Optimal levels represent those that produce a
maximal risk reduction through reasonably
available therapies
• Goals of therapy depend on clinical judgment
and are based on projected efficacy, cost-
effectiveness, and safety of available therapies
• When drug therapies are employed, optimal
levels usually represent a reasonable goal of
therapy
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Lifestyle Therapies:
LDL-Raising Lipids
• Reduce intake of saturated fatty acids to <
7% of total calories, and at least to < 10%
• Lower intake of trans fatty acids to < 1% of
total calories
• Reduce dietary cholesterol to < 200 mg/day
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Lifestyle Therapies:
Total Fat • The IAS recommends flexibility in the intake of total fat
depending on cultural preferences, such as:
– Lower fat intakes of 20-25% of calories or even lower
(as is typical in Pacific Rim countries)
– Or higher fat intakes of 30-35% of calories or even
higher (as is typical in Mediterranean countries)
• Any fat intake above the recommended for saturated and
trans fatty acids should be in the form of unsaturated
fatty acids
• Irrespective of the total fat content of the diet, nutrient
needs must be met and energy intake should be
appropriate for maintenance of a healthy body weight
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Lifestyle Therapies:
Total Calories
• Body mass index (BMI) should be
measured in all patients
• Control intake of total calories to achieve
and maintain a desirable weight
• If desirable weight is defined by BMI,
employ national standards for BMI
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Lifestyle Therapies:
Other Dietary Factors • Maintain relatively high intakes of fruits, vegetables, and
fiber
• Replace excess saturated fatty acids with either complex,
fiber-rich carbohydrates (with emphasis on whole grains)
or monounsaturated/polyunsaturated fatty acids
• Consume some fish rich in n-3 fatty acids
• Other cardioprotective foods include nuts, seeds, and
vegetable oils
• Consider using plant sterols/stanols (2 g/day) and
soluble/viscous fiber (10 to 25 g/day) as a dietary adjunct
to further lower LDL-C levels
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Lifestyle Therapies:
Other Dietary Factors
• Eat foods low in sodium and high in potassium
• Dietary sodium should be less than 2 g per day
and < 1500 mg for individuals at risk
• For individuals who choose to consume alcohol,
not more than 2 servings daily for men and 1
serving daily for women is advised
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Lifestyle Therapies:
Physical Activity
• Engage in approximately 30 minutes of
moderate intensity physical activity daily
• The activity should be aerobic, 40-75% of
aerobic capacity, for 5-7 days a week, for 30-60
minutes per day
• For individuals trying to lose weight it is
recommended that these individuals eventually
progress to higher amounts of exercise (e.g.
250-300 min/week or > 2000 kcal/week of
leisure-time physical activity)
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Metabolic syndrome
• The metabolic syndrome is a multiplex risk factor
for ASCVD
• Obesity and physical inactivity contribute
importantly to development of the metabolic
syndrome
• For patients with this syndrome, weight
reduction and increased physical activity can
reduce metabolic risk factors
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
© 2013 International Atherosclerosis Society. All rights reserved.
Criteria for Clinical Diagnosis
of the Metabolic Syndrome Measures Categorical Cut Points
Elevated Waist Circumference Population- and country-specific
definitions
Elevated triglycerides > 150 mg/dL (1.7 mmol/L)
Reduced HDL-C < 40 mg/dL (1.0 mmol/L) in males
< 50 mg/dL (1.3 mmol/L) in females
Elevated blood pressure Systolic > 130 and/or diastolic > 85
mm Hg
Elevated fasting glucose > 100 mg/dL
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Population Male
(cm)
Female
(cm)
Population Male
(cm)
Female
(cm)
Asian ≥ 90 ≥ 80 Canadian ≥ 102 ≥ 88
Chinese ≥ 85 ≥ 80 Ethnic Central
and So. American
≥ 94 ≥ 80
European ≥ 94 or
≥ 102
≥ 80 or
≥ 88
Middle Eastern,
Mediterranean
≥ 94 ≥ 80
Japanese ≥ 85 ≥ 90 Sub-Saharan
African
≥ 94 ≥ 80
USA ≥ 102 ≥ 88 © 2013 International Atherosclerosis Society. All rights reserved.
Current Recommended Waist Circumference
Thresholds for Abdominal Obesity
Drug Therapy for Primary
Prevention • Statins are first line therapy for achieving the optimal
levels of atherogenic cholesterol in higher risk persons
• In those who are statin intolerant, several options are
available: switching statins, reducing statin dose, every
other day statins, use of alternate drugs (ezetimibe, bile
acid resins, niacin) alone or in combination, and
maximizing lifestyle intervention
• When drugs are used for primary prevention, intensity of
therapy should be sufficient to achieve optimal levels of
atherogenic cholesterol
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Secondary Prevention: Achieving an
Optimal Atherogenic Cholesterol Level
• The optimal LDL-C in patients with established
ASCVD is < 70 mg/dL (1.8 mmol/L) (or non-
HDL-C of < 100 mg/dL [2.6 mmol/L])
• Most patients with ASCVD deserve maximal
statin therapy when it is tolerated
• To achieve an LDL-C < 70 mg/dL (1.8 mmol/L)
some patients will require add-on drugs to
statins (i.e. ezetimibe and/or bile acid resins)
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Secondary Prevention:
Intolerance to High-Dose Statins
• In patients who cannot tolerate high-dose
statins, an alternative is to combine a
moderate dose of statin with either
ezetimibe or bile acid-binding resin
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Secondary Prevention: Patients
with Hypertriglyceridemia
• For those with high triglycerides, nicotinic acid or
a fibrate are alternative add-on drugs
• However, risk reduction with combined drug
therapy comparable to that with high-dose
statins has not been documented in RCTs
• Subgroup analysis of RCTs and atherosclerosis
imaging provides some evidence of benefit of
combined drug therapy
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Secondary Prevention: Importance
of Maximal Lifestyle Therapy
• Even in patients who are treated with
maximal cholesterol-lowering drugs,
lifestyle therapies should be continued and
emphasized
• Maximal lifestyle therapies have the
potential to give additional risk reduction
beyond drug therapy
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
Secondary Prevention: Full
Attention to Non-Lipid Risk Factors
• Cigarette smoking
• Hypertension
• Diabetes mellitus
• Obesity
• Physical inactivity
• Prothrombotic state
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org
IAS Panel Members
• Scott M. Grundy (Chair)
• Hidenori Arai
• Philip Barter
• Thomas P. Bersot
• D. John Betteridge
• Rafael Carmena
• Ada Cuevas
• Michael H. Davidson
• Jacques Genest
• Y. Antero Kesäniemi
• Shaukat Sadikot
• Raul D. Santos
• Andrey Susekov
• Rody Sy
• Lale Tokgozoglu
• Gerald F. Watts
• Dong Zhao
© 2013 International Atherosclerosis Society. All rights reserved. www.athero.org